EVIDENCE SUMMARY
Benzodiazepines work—but how do they compare?
A 2010 Cochrane meta-analysis of 64 RCTs and controlled clinical trials (CCTs; N = 4309) evaluated the use of benzodiazepines for treatment of AWS in adults.1 This systematic review compared benzodiazepines
- vs placebo (10 studies)
- vs other drugs, including phenobarbital, carbamazepine, topiramate, lamotrigine, gabapentin, haloperidol, clonidine, hydroxyzine, propranolol, and baclofen (42 studies)
- to other benzodiazepines, including chlordiazepoxide, alprazolam, diazepam, and lorazepam (18 studies)
- in combination with other drugs vs other drugs alone (3 studies)
- administered on a fixed schedule vs symptom-triggered administration (3 studies).
Primary outcomes included efficacy (alcohol withdrawal seizures, alcohol withdrawal delirium, alcohol withdrawal symptoms, global improvement), safety (adverse events and severe, life-threatening adverse events), and acceptability (dropouts and dropouts due to adverse events).
Benzodiazepines performed better than placebo for seizures in 3 studies (N = 324), with a relative risk (RR) of 0.16 (95% confidence interval [CI], 0.04-0.69). Studies assessing the described outcomes between benzodiazepines and other drugs were often of small sample size and heterogeneous in interventions and outcomes, limiting the ability to draw clear conclusions regarding benzodiazepine superiority. Comparisons of different benzodiazepines with each other and comparisons of benzodiazepines combined with other drugs vs other drugs alone did not reach statistical significance. Data on harms of benzodiazepines were lacking.
Anticonvulsants are not better than placebo for AWS
Another 2010 Cochrane meta-analysis of 56 RCTs and CCTs (N = 4076) evaluated the use of anticonvulsants for AWS.2 This systematic review compared anticonvulsants
- vs placebo (17 studies)
- vs other drugs, such as bromocriptine, piracetam, gamma-hydroxybutyric acid, trifluoperazine, clonidine, and various benzodiazepines (32 studies)
- to other anticonvulsants (10 studies)
- in combination with other drugs vs other drugs alone (6 studies)
- in combination with other drugs vs different anticonvulsants (1 study).
Primary outcomes included reductions in alcohol withdrawal seizures, adverse events, and acceptability of medication as indicated by participant dropouts.
Anticonvulsants were not superior to placebo for any outcome. Three studies (N = 260) favored carbamazepine over benzodiazepine (oxazepam or lorazepam) for 1 secondary outcome: a reduction of Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar) score (maximum score of 7; mean difference [MD] = –1 [95% CI, –1.9 to –0.2]).
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